Mahshid Yilmaz, Lisy Marcus-René, Wang Xiao, Spanbroek Rainer, Flygare Jenny, Christensson Birger, Björkholm Magnus, Sander Birgitta, Habenicht Andreas J R, Claesson Hans-Erik
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
BMC Immunol. 2009 Jan 9;10:2. doi: 10.1186/1471-2172-10-2.
Human B lymphocytes can produce leukotriene B4 but the biological function of the 5-lipoxygenase (5-LO) pathway in B cells is unclear. In order to better understand and define the role of 5-LO in B cells, we investigated the expression of 5-LO mRNA and protein in subsets of B cells from human tonsils and different types of B cell lymphoma.
Based on RT-PCR and western blot/immunohistochemical staining, with a polyclonal antibody raised against 5-LO, high expression of 5-LO was found in mantle zone B cells from tonsils. By contrast, only a weak expression of 5-LO was detected in germinal centre cells and no expression in plasma cells from tonsils. This pattern of 5-LO expression was preserved in malignant lymphoma with high expression in mantle B cell lymphoma (MCL) and weak or no expression in follicular lymphoma. Primary leukemized MCL, so called B-prolymphocytic leukaemia cells, and MCL cell lines also expressed 5-LO and readily produced LTB4 after activation.
The present report demonstrates the expression of 5-LO mainly in normal and malignant mantle zone B cells while the expression is low or absent in germinal centre B cells and plasma cells, indicating a role of the 5-LO pathway in B cells before the cells finally differentiate to plasma cells.
人类B淋巴细胞可产生白三烯B4,但B细胞中5-脂氧合酶(5-LO)途径的生物学功能尚不清楚。为了更好地理解和界定5-LO在B细胞中的作用,我们研究了人扁桃体B细胞亚群以及不同类型B细胞淋巴瘤中5-LO mRNA和蛋白的表达情况。
基于逆转录聚合酶链反应(RT-PCR)以及蛋白质免疫印迹/免疫组织化学染色,使用针对5-LO的多克隆抗体,发现扁桃体套区B细胞中5-LO高表达。相比之下,生发中心细胞中仅检测到5-LO弱表达,扁桃体浆细胞中未检测到表达。这种5-LO表达模式在恶性淋巴瘤中得以保留,套细胞淋巴瘤(MCL)中高表达,滤泡性淋巴瘤中弱表达或不表达。原发性白血病化的MCL,即所谓的B原淋巴细胞白血病细胞,以及MCL细胞系也表达5-LO,激活后可轻易产生白三烯B4(LTB4)。
本报告表明5-LO主要在正常和恶性套区B细胞中表达,而生发中心B细胞和浆细胞中表达低或无表达,这表明5-LO途径在B细胞最终分化为浆细胞之前发挥作用。